HBV is a virus having DNA genomes belonging to Hepadnaviridae family and causes acute and/or chronic hepatitis. In general, HBV is classified into eight genotypes which have at least 8% different gene sequences to one another or, otherwise, divided into nine serotypes (i.e., adw, adr, ayw, ayr, or the like) on the basis of two antigenic determinants (that is, epitopes) (d/y, w/r) of HBV surface antigen (HBsAg). 350 million people worldwide have been infected with chronic HBV and, specifically, about 5 to 8% of the population in Korea and China has chronic HBV infection. HBV infection is a major cause of liver diseases and liver cancer in these regions. At present, although the above infection can be protected somewhat by the development of vaccines, lots of patients still suffer from chronic Hepatitis B infection caused by HBV. HBV-caused chronic infection may induce hepatitis as well as liver cirrhosis and liver cancer and, as compared to non-infected people, people with chronic infection show an increase in liver cancer about 300 times higher. According to WHO investigation, chronic hepatitis B is considered as a major cause of about 80% of liver cancers.
Chronic hepatitis B medicine recently developed as a nucleoside analogue and available on the market may include, for example, lamivudine, adefovir dipivoxil, etc. These medicines may interfere with a reverse transcriptase of HBV polymerase, in turn inhibiting HBV DNA replication. However, in the case where any one of the foregoing medicines is administered for a long term such as 3 years, about 75% of the patients have drug resistance viruses, thus entailing a problem of deterioration in the curing efficacy. In order to prevent vertical transmission or infection after liver transplantation, the foregoing medicines are commonly used with hepatitis B immunoglobulin (HBIG).
Currently HBIG is manufactured by ion-exchange purification and virus inactivation from plasma of donors with high anti-HBsAg antibody titer.
However, the currently available HBIG is not an ideal source of therapeutic antibody due to its limited availability, low specific activity and possible contamination of infectious agents.
It is known that antibodies generated in vivo by vaccines now used in the art are mostly antibodies recognizing ‘a’ epitope of HBV. However, mutants escaping such antibodies, for example, a G145R mutant generated by substituting glycine at 145 of the HBsAg with arginine has recently been reported. Additionally, a variety of escaping mutants have also been found, therefore, existing HBV medicines involve limitations in rendering satisfactory curing efficacy. Accordingly, there is an increasing demand for HBV treatment antibodies and/or HBV vaccines specifically bound to epitopes that correspond to sites necessary for the survival of HBV in association with HBV replication and does not cause mutation, thus not causing deterioration in curing efficacy due to mutation.